IDR‐1018 induces cell proliferation, migration, and reparative gene expression in 2D culture and 3D human skin equivalents

2019 ◽  
Vol 13 (11) ◽  
pp. 2018-2030
Author(s):  
Thuany Alencar‐Silva ◽  
Alessandra Zonari ◽  
Daniel Foyt ◽  
Mylieneth Gang ◽  
Robert Pogue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Human Skin ◽  
Skin Equivalents

scholarly journals Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

2021 ◽  
Vol 22 (4) ◽  
pp. 2160
Author(s):  
Kyunghee Kim ◽  
Jisue Kim ◽  
Hyoungseob Kim ◽  
Gun Yong Sung
Keyword(s):  
Gene Expression ◽  
Human Skin ◽  
Lipoic Acid ◽  
Drug Testing ◽  
Structural Integrity ◽  
Microfluidic Channel ◽  
Skin Barrier Function ◽  
Animal Testing ◽  
Epidermal Structure ◽  
Skin Equivalents

Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.

scholarly journals Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71143 ◽  
Author(s):  
Marjorie S. Morgan ◽  
Larry G. Arlian ◽  
Michael P. Markey
Keyword(s):  
Gene Expression ◽  
Human Skin ◽  
Sarcoptes Scabiei ◽  
Skin Equivalents

ACE INHIBITION ATTENUATES RENAL PDGF GENE EXPRESSION AND CELL PROLIFERATION IN SUBTOTAL NEPHRECTOMY

Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A104-A104
Author(s):  
Jandeleit‐Dahm K ◽  
Wu Ll ◽  
Johnson Rj ◽  
Cox Aj ◽  
Kelly Dj ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Ace Inhibition ◽  
Subtotal Nephrectomy

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

scholarly journals The Potential of 2-aza-8-Oxohypoxanthine as a Cosmetic Ingredient

Cosmetics ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 60
Author(s):  
Hisae Aoshima ◽  
Masayuki Ito ◽  
Rinta Ibuki ◽  
Hirokazu Kawagishi
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Microarray Analysis ◽  
Dna Microarray ◽  
Cell Activation ◽  
Skin Barrier ◽  
Efficacy Evaluation ◽  
Activation Effect ◽  
Expression Levels ◽  
Dna Microarray Analysis

In this study, we verified the effects of 2-aza-8-oxohypoxanthine (AOH) on human epidermal cell proliferation by performing DNA microarray analysis. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, which measures mitochondrial respiration in normal human epidermal keratinocyte (NHEK) cells. Gene expression levels were determined by DNA microarray analysis of 177 genes involved in skin aging and disease. AOH showed a significant increase in cell viability at concentrations between 7.8 and 31.3 μg/mL and a significant decrease at concentrations above 250 μg/mL. DNA microarray analysis showed that AOH significantly increased the gene expression of CLDN1, DSC1, DSG1, and CDH1 (E-cadherin), which are involved in intercellular adhesion and skin barrier functioning. AOH also up-regulated the expression of KLK5, KLK7, and SPIMK5, which are proteases involved in stratum corneum detachment. Furthermore, AOH significantly stimulated the expression of KRT1, KRT10, TGM1, and IVL, which are considered general differentiation indicators, and that of SPRR1B, a cornified envelope component protein. AOH exerted a cell activation effect on human epidermal cells. Since AOH did not cause cytotoxicity, it was considered that the compound had no adverse effects on the skin. In addition, it was found that AOH stimulated the expression levels of genes involved in skin barrier functioning by DNA microarray analysis. Therefore, AOH has the potential for practical use as a cosmetic ingredient. This is the first report of efficacy evaluation tests performed for AOH.

scholarly journals Mechanical and Immunological Regulation in Wound Healing and Skin Reconstruction

2021 ◽  
Vol 22 (11) ◽  
pp. 5474
Author(s):  
Shun Kimura ◽  
Takashi Tsuji
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Human Skin ◽  
Developmental Stages ◽  
Control Mechanisms ◽  
Tissue Remodelling ◽  
Skin Equivalents ◽  
Immunological Interactions ◽  
Stress Signals ◽  
Specific Species

In the past decade, a new frontier in scarless wound healing has arisen because of significant advances in the field of wound healing realised by incorporating emerging concepts from mechanobiology and immunology. The complete integumentary organ system (IOS) regeneration and scarless wound healing mechanism, which occurs in specific species, body sites and developmental stages, clearly shows that mechanical stress signals and immune responses play important roles in determining the wound healing mode. Advances in tissue engineering technology have led to the production of novel human skin equivalents and organoids that reproduce cell–cell interactions with tissue-scale tensional homeostasis, and enable us to evaluate skin tissue morphology, functionality, drug response and wound healing. This breakthrough in tissue engineering has the potential to accelerate the understanding of wound healing control mechanisms through complex mechanobiological and immunological interactions. In this review, we present an overview of recent studies of biomechanical and immunological wound healing and tissue remodelling mechanisms through comparisons of species- and developmental stage-dependent wound healing mechanisms. We also discuss the possibility of elucidating the control mechanism of wound healing involving mechanobiological and immunological interaction by using next-generation human skin equivalents.

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